This project concerns clinical, preclinical and biophysical studies of anticancer drugs. A clinically useful assay for citrovorum factor and 5'methyltetrahydrafolic acid has been developed and applied to clinical situations. Preclinical studies utilizing a primate model have also been done using this assay. Other preclinical studies of systemic and cerebrospinal pharmacokinetics have been initiated using a variety of anti-neoplastic drugs. Drug-drug interactions have also been explored using this model. The alkaline elution technique (Kohn and Ewing, Biochemistry 1974) has been employed in a study of the interaction of intercalating agents with nucleic acids in vitro (i.e., cells). Such intercalating agents have included adriamycin, daunomycin, eliptocine and actinomycin D. Light-sensitive photoreactions with DNA by certain intercalating agents, the psoralens, have also been studied using this technique. Physico-chemical meaurements, including electric dichroism and hydrodynamic studies, have also been initiated on these compounds and their derivatives. The object of these studies is to be able to employ such compounds as therapeutic agents and to utilize compounds such as these with known mechanisms of action, as probes in examining the mechanisms of action of other chemotherapeutic agents whose mechanisms are not defined.